Pseudophosphatases as Regulators of MAPK Signaling.

Emma Marie Wilber Hepworth,Shantá D Hinton

doi:10.3390/ijms222212595

Abstract

Mitogen-activated protein kinase (MAPK) signaling pathways are highly conserved regulators of eukaryotic cell function. These enzymes regulate many biological processes, including the cell cycle, apoptosis, differentiation, protein biosynthesis, and oncogenesis; therefore, tight control of the activity of MAPK is critical. Kinases and phosphatases are well established as MAPK activators and inhibitors, respectively. Kinases phosphorylate MAPKs, initiating and controlling the amplitude of the activation. In contrast, MAPK phosphatases (MKPs) dephosphorylate MAPKs, downregulating and controlling the duration of the signal. In addition, within the past decade, pseudoenzymes of these two families, pseudokinases and pseudophosphatases, have emerged as bona fide signaling regulators. This review discusses the role of pseudophosphatases in MAPK signaling, highlighting the function of phosphoserine/threonine/tyrosine-interacting protein (STYX) and TAK1-binding protein (TAB 1) in regulating MAPKs. Finally, a new paradigm is considered for this well-studied cellular pathway, and signal transduction pathways in general.

Highlights

Mitogen-activated protein kinase (MAPK) signaling pathways are highly conserved regulators of eukaryotic cell function
Post-translational modifications (PTMs) of proteins play a role in the complexity of signaling networks
The most common phosphorylation events occur on serine, threonine, and tyrosine residues [4]

Summary

Introduction

Mitogen-activated protein kinase (MAPK) signaling pathways are highly conserved regulators of eukaryotic cell function. Mitogen-activated protein kinase (MAPK) signaling pathways are important regulators in cellular processes such as survival, proliferation, apoptosis, and differentiation [8]. Pathways, including extracellular signal-regulated (ERK1/2); c-JUN NH2 -terminus kinase or stress protein-activated kinases (JNKs/SAPKs); and p38 MAPK [9]. Certain pseudophosphatases have been shown to be regulators of MAPK signaling, highlighting the timeliness of this special edition, Mitogen-Activated Kinases: New Insights for Old Cell Signaling Pathways.

Results

Conclusion